We read this article with interest [1]; we ask for some clarification and share a few comments. The authors mention that the pathologist confirmed the zonal origin of the prostate tissues studied (i.e. peripheral zone, PZ, or transition zone, TZ). Although morphological differences between the PZ and TZ were reported previously [2], many pathologists would agree that it is extremely difficult to differentiate between these prostate-tissue zones just on the basis of visual discrimination after staining with haematoxylin and eosin (H&E); a morphological distinguishing factor might be that the stromal component often constitutes a greater proportion of the TZ than the much higher concentration of glandular elements in the PZ. We are interested in ascertaining whether the authors used other novel techniques to confirm the zone of origin.

The differential gene expression patterns between these prostate zones might be simply a consequence of such distinguishing morphological differences. However, this study seemed to suggest that zone-specific gene expression profiles are identifiable despite the current lack of discriminating epithelial cell or stromal markers that might validate the precise location from which the tissue was isolated. Prostate adenocarcinoma occurs far more frequently in the PZ than the TZ; this study also lends weight to the notion that susceptibility markers underlying the progression of prostate cancer might ultimately be identified using this approach.

Other studies have also indicated differences between these prostate zones. Divergent hormone responsiveness of primary cultures of putative PZ- and TZ-derived stem cells [3] and in the inter-zone differential expression of certain hormone-metabolising enzymes (e.g. CYP1B1) [4] have been suggested. Discriminating between genes that are differentially expressed in a normal-functioning gland and those that might have altered transcription associated with elevated susceptibility to progression of prostate cancer remains an important challenge.